The overarching goal of this K24 application is to further my development as a clinical investigator and support the training of future physician scientists. My patient oriented research interests relate to understanding the clinical, pathologic, genetic and pathomechanistic underpinnings of inherited and acquired forms of muscle weakness. With the support of this grant, I will continue to perform genetic discovery of patients with muscle disease, increase our biorepository and develop phenotypic assays to understand novel disease pathogenesis. In addition, I will increase my mentorship responsibilities of graduate students, resident physicians, fellows and junior faculty within the neuromuscular group and Department of Neurology at Washington University School of Medicine. Moreover, I will learn valuable skills related to whole genome sequencing, RNA sequencing and induce pluripotent stem cell differentiation. A K24 grant would protect 50% effort and relieve future clinical and administrative responsibilities. The two interrelated aims of this proposal are 1) Perform genetic discovery on patients with unresolved inherited and acquired myopathies using whole genome and RNA sequencing strategies. 2) Develop and phenotype iPSC derived myoblast models of inherited and acquired myopathies. These aims will be achieved utilizing our existing biorepository within the Washington University School of Medicine Neuromuscular Genetics Project and the acquisition of new patients and patient material. Support through a K24 Midcareer Investigator Award in Patient-Oriented Research would come at a critical time in my career as I solidify my independent research program and increase my availability to mentor graduate students, post- doctoral fellows, residents, neuromuscular fellows and junior faculty in translational myology. Upon completion of this award, I will have integrated clinical trainees into our existing translational research infrastructure and created a successful pipeline to generate the next generation of clinician-scientists focused on muscle diseases.